title: A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression.
abstract: BACKGROUND
  Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression. This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role.
  
  
  METHODS
  In this multicenter trial, conducted at 19 sites, patients aged 18-65 years with a DSM-IV/ICD-10 diagnosis of unipolar, nonpsychotic major depressive disorder (confirmed by the Mini-International Neuropsychiatric Interview) who had failed at least 1 adequate trial of an antidepressant (N = 183) were first treated for 8 weeks with open-label paroxetine or paroxetine controlled-release in dosages up to 50 mg/d or 62.5 mg/d, respectively. Individuals with a 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 (n = 96) were then randomized on a double-blind basis to receive either placebo or lamotrigine in dosages titrated upward to a maximum of 400 mg/d for 10 weeks. Sixty-five patients completed the study. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS), and the main secondary outcome measures were the HDRS-17 and Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) ratings. Data were collected from 2003 to 2006.
  
  
  RESULTS
  Results of the primary efficacy analysis of the randomized patients using the MADRS, HDRS-17, CGI-S, and CGI-I did not demonstrate a statistically significant difference between lamotrigine and placebo groups, although some secondary analyses were suggestive of efficacy, particularly in those patients who completed the study (completer analysis) and in more severely ill patients (HDRS-17 ≥ 25).
  
  
  CONCLUSIONS
  This add-on study of patients with treatment-resistant depression failed to detect a statistically significant difference between lamotrigine and placebo given for 10 weeks. However, post hoc analyses suggest that future studies of lamotrigine's efficacy might focus on specific subgroups with depression.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00901407.
authors.affiliation: Department of Psychiatry, Louisiana State University Health Sciences Center, New Orleans, LA, USA. jgbmd@att.net
authors.forename: James G
authors.initials: JG
authors.lastname: Barbee
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Thompson
authors.forename: Nowal J
authors.initials: NJ
authors.lastname: Jamhour
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Stewart
authors.forename: Erich J
authors.initials: EJ
authors.lastname: Conrad
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Reimherr
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D014227:Triazines; D017374:Paroxetine; D000077213:Lamotrigine